Fish and Omega-3 Fatty Acids: Sex and Racial Differences in Cardiovascular Outcomes and Cognitive Function.

Both cardiovascular disease (CVD) and cognitive decline are common features of aging. One in 5 deaths is cardiac for both men and women in the United States, and an estimated 50 million are currently living with dementia worldwide. In this review, we summarize sex and racial differences in the role of fish and its very long chain omega-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in preventing CVD events and cognitive decline. In prospective studies, women with higher nonfried and fatty fish intake and women and Black individuals with higher plasma levels of EPA and DHA had a lower risk of CVD. In randomized controlled trials of EPA and DHA supplementation in primary CVD prevention, Black subjects benefited in a secondary outcome. In secondary CVD prevention, both men and women benefited, and Asians benefited as a prespecified subgroup. Fish and omega-3 polyunsaturated fatty acids are associated with prevention of cognitive decline in prospective studies. In randomized controlled trials of EPA and DHA supplementation, women have cognitive benefit. DHA seems more beneficial than EPA, and supplementation is more beneficial when started before cognitive decline. Although studies in women and racial groups are limited, life-long intake of nonfried and fatty fish lowers the risk of CVD and cognitive decline, and randomized controlled trials also show the benefit of EPA and DHA supplementation. These findings should be factored into recommendations for future research and clinical recommendations as dietary modalities could be cost-effective for disease prevention.

Eicosapentaenoic and docosahexaenoic acid supplementation and coronary artery calcium progression in patients with coronary artery disease: A secondary analysis of a randomized trial.

BACKGROUND AND AIMS: We previously reported that an omega-3 fatty acid index ≥4% with high-dose eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) prevented progression of noncalcified plaque. Higher coronary artery calcium (CAC) scores and progression of CAC are associated with increased cardiovascular events and mortality. We examined the effect of EPA + DHA on CAC score. METHODS: A total of 242 patients with coronary artery disease (CAD) on statin therapy were randomized to 1.86 g EPA and 1.5 g DHA daily or none (control) for 30 months. The CAC score was measured at baseline and 30-months with non-contrast, cardiac computed tomography. RESULTS: Both EPA + DHA and control groups had significant progression in CAC scores over 30 months (median change:183.5 vs 221.0, respectively, p < 0.001) despite a 13.6% reduction in triglyceride level with EPA + DHA. No significant difference was observed between groups for the total group, by baseline CAC scores of <100, 100-399, 400-999 and ≥1000 or quartiles of achieved levels of EPA, DHA and the omega-3 fatty acid index. Similar rates of CAC progression were noted in those on high-intensity statin compared to low- and moderate-intensity statin. CONCLUSIONS: EPA and DHA added to statin resulted in similar CAC progression over 30 months regardless of baseline CAC categories, statin intensity and achieved levels of EPA, DHA and the omega-3 fatty acid index.

Case report: Coronary atherosclerosis in a patient with long-standing very low LDL-C without lipid-lowering therapy.

Background: ApoB-containing lipoproteins including low-density lipoprotein cholesterol (LDL-C) are necessary for the development of atherosclerosis, and lifelong exposure to low serum levels of LDL-C have been associated with a substantial reduction of cardiovascular risk. Although plaque regression has been observed in patients with serum LDL-C less than 70-80 mg/dl on lipid-lowering therapy, an LDL-C level under which atherosclerosis cannot develop has not been established. Case presentation: In this case we describe a 60-year-old man with well-controlled diabetes mellitus and hypertension who presented to the hospital after an acute stroke likely due to an atrial myxoma discovered on imaging. A coronary computed tomography angiography scan performed in preparation for the planned surgical myxoma resection revealed an anomalous origin of the right coronary artery as well as evidence of nonobstructive coronary atherosclerosis in the right coronary and non-anomalous left coronary system. Despite not having ever been on any lipid-lowering therapy, this patient was found to have low LDL-C levels (<40 mg/dl) during this admission and on routine laboratory data collected over the prior 16 years. His family history strongly suggested heterozygous familial hypobetalipoproteinemia as a possible diagnosis. Conclusions: This case illustrates that even long-standing, very low levels of LDL-C may be insufficient to completely prevent atherosclerosis and emphasizes the importance of primordial prevention of all cardiovascular risk factors.

Omega-3 Fatty Acids as Antiarrhythmic Drugs: Upstream Target Modulators Affecting Acute and Long-Term Pathological Alterations in Cardiac Structure and Function.

OBJECTIVES: Postoperative atrial fibrillation (POAF) is a common complication in the acute care period following coronary artery bypass grafting (CABG) surgery that is associated with significant morbidity and mortality in both short-term and long-term settings. Recently, the Vaughn Williams Classification of antiarrhythmic agents, first proposed in 1975 and widely viewed as the authoritative description of their electrophysiologic actions, was updated and notably omega-3 fatty acids (Ω-3 fatty acids) have been included in class VII, described as "upstream target modulators," to mitigate pathological structural and electrophysiological remodeling changes in the aged and/or injured myocardium. DATA SOURCES: A PubMed literature search was performed. STUDY SELECTION: Studies examining the significance of complications in patients undergoing isolated CABG surgery were selected for inclusion. DATA EXTRACTION: Relevant data were qualitatively assessed and narratively summarized. DATA SYNTHESIS: POAF occurs in approximately 30% of patients, and inflammation from chronic coronary artery disease preoperatively, as well as acute atrial inflammation from surgery postoperatively are the leading causes. Inflammation underlies its pathophysiology; therefore Ω-3 fatty acids not only exhibit antiarrhythmic properties but are an effective anti-inflammatory treatment that may reduce the clinical risks of POAF. CONCLUSIONS: At present no effective prophylaxis is available to address POAF following CABG surgery. Clinical approaches that focus on the inflammatory response in this setting may optimize the response to treatment. The current literature supports the hypothesis that Ω-3 fatty acids may acutely reduce the inflammatory response via favorable alterations in the metabolism of prostaglandins and leukotrienes (eicosanoids) and specialized pro-resolving mediators.

Regression of Coronary Fatty Plaque and Risk of Cardiac Events According to Blood Pressure Status: Data From a Randomized Trial of Eicosapentaenoic Acid and Docosahexaenoic Acid in Patients With Coronary Artery Disease.

Background Residual risk of cardiovascular events and plaque progression remains despite reduction in low-density lipoprotein cholesterol. Factors contributing to residual risk remain unclear. The authors examined the role of eicosapentaenoic acid and docosahexaenoic acid in coronary plaque regression and its predictors. Methods and Results A total of 240 patients with stable coronary artery disease were randomized to eicosapentaenoic acid plus docosahexaenoic acid (3.36 g/d) or none for 30 months. Patients were stratified by regression or progression of coronary fatty plaque measured by coronary computed tomographic angiography. Cardiac events were ascertained. The mean±SD age was 63.0±7.7 years, mean low-density lipoprotein cholesterol level was <2.07 mmol/L, and median triglyceride level was <1.38 mmol/L. Regressors had a 14.9% reduction in triglycerides that correlated with fatty plaque regression (r=0.135; P=0.036). Compared with regressors, progressors had higher cardiac events (5% vs 22.3%, respectively; P<0.001) and a 2.89-fold increased risk of cardiac events (95% CI, 1.1-8.0; P=0.034). Baseline non-high-density lipoprotein cholesterol level <2.59 mmol/L (100 mg/dL) and systolic blood pressure <125 mm Hg were significant independent predictors of fatty plaque regression. Normotensive patients taking eicosapentaenoic acid plus docosahexaenoic acid had regression of noncalcified coronary plaque that correlated with triglyceride reduction (r=0.35; P=0.034) and a significant decrease in neutrophil/lymphocyte ratio. In contrast, hypertensive patients had no change in noncalcified coronary plaque or neutrophil/lymphocyte ratio. Conclusions Triglyceride reduction, systolic blood pressure <125 mm Hg, and non-high-density lipoprotein cholesterol <2.59 mmol/L were associated with coronary plaque regression and reduced cardiac events. Normotensive patients had greater benefit than hypertensive patients potentially due to lower levels of inflammation. Future studies should examine the role of inflammation in plaque regression. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01624727.

Higher exercise capacity, but not omega-3 fatty acid consumption, predicts lower coronary artery calcium scores in women and men with coronary artery disease.

BACKGROUND AND AIMS: Higher coronary artery calcium (CAC) scores are associated with increased cardiovascular (CVD) events and mortality. Exercise capacity is predictive of CVD events. Our aim was to examine the relationship between exercise capacity and CAC in women and men. METHODS: CAC was measured in 203 men and 38 women with clinical coronary artery disease using multidetector coronary tomography. They were randomized to 3.36 g eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) daily or none for 30 months. Maximal exercise treadmill testing was performed at baseline with calculation of metabolic equivalents of task (METs) achieved as a measure of exercise capacity. RESULTS: Despite similar ages at baseline (64.0 ± 6.7 vs 62.7 ± 7.8 years, respectively, p = 0.225), women had lower CAC scores compared to men: 106.7 Agatston units [AU] vs 535.3, respectively, p < 0.001, and at every age (p < 0.001). Female CAC scores did not equal those of men until women were 20 years older. Higher levels of METs were associated with lower CAC scores in both women and men. After multivariate adjustment, METs was the most important predictor of CAC score in women at baseline and 30 months (p = 0.001 and 0.029, respectively) whereas only age predicted in men (p = 0.019 and 0.004, respectively). Annual CAC progression was significantly greater in men compared to women (94.8 AU/year vs 38.0, respectively, p = 0.014). No difference was observed in CAC progression in the EPA + DHA group compared to control in either men or women. CONCLUSIONS: The association of higher METs with lower CAC scores in both women and men supports recommending exercise to maximize cardiorespiratory fitness as this may minimize CAC scores and thus, potentially decrease risk for CVD events. This may be especially important for women since METs independently predicted baseline and 30 month CAC in women.

Sex-Specific Differences in Lipoprotein Production and Clearance.

Therapeutic approaches to reduce atherogenic lipid and lipoprotein levels remain the most effective and assessable strategies to prevent and treat cardiovascular disease. The discovery of novel research targets linked to pathways associated with cardiovascular disease development has enhanced our ability to decrease disease burden; however, residual cardiovascular disease risks remain. Advancements in genetics and personalized medicine are essential to understand some of the factors driving residual risk. Biological sex is among the most relevant factors affecting plasma lipid and lipoprotein profiles, playing a pivotal role in the development of cardiovascular disease. This minireview summarizes the most recent preclinical and clinical studies covering the effect of sex on plasma lipid and lipoprotein levels. We highlight the recent advances in the mechanisms regulating hepatic lipoprotein production and clearance as potential drivers of disease presentation. We focus on using sex as a biological variable in studying circulating lipid and lipoprotein levels.

Sex, Racial, and Ethnic Disparities in Acute Coronary Syndrome: Novel Risk Factors and Recommendations for Earlier Diagnosis to Improve Outcomes.

In this review, sex, racial, and ethnic differences in acute coronary syndromes on a global scale are summarized. The relationship between disparities in presentation and management of acute coronary syndromes and effect on worse clinical outcomes in acute coronary syndromes are discussed. The effect of demographic, geographic, racial, and ethnic factors on acute coronary syndrome care disparities are reviewed. Differences in risk factors including systemic inflammatory disorders and pregnancy-related factors and the pathophysiology underlying them are discussed. Finally, breast arterial calcification and coronary calcium scoring are discussed as methods to detect subclinical atherosclerosis and start early treatment in an attempt to prevent clinical disease.

Epidemiology of Diabetes and Atherosclerotic Cardiovascular Disease Among Asian American Adults: Implications, Management, and Future Directions: A Scientific Statement From the American Heart Association.

Asian American individuals make up the fastest growing racial and ethnic group in the United States. Despite the substantial variability that exists in type 2 diabetes and atherosclerotic cardiovascular disease risk among the different subgroups of Asian Americans, the current literature, when available, often fails to examine these subgroups individually. The purpose of this scientific statement is to summarize the latest disaggregated data, when possible, on Asian American demographics, prevalence, biological mechanisms, genetics, health behaviors, acculturation and lifestyle interventions, pharmacological therapy, complementary alternative interventions, and their impact on type 2 diabetes and atherosclerotic cardiovascular disease. On the basis of available evidence to date, we noted that the prevalences of type 2 diabetes and stroke mortality are higher in all Asian American subgroups compared with non-Hispanic White adults. Data also showed that atherosclerotic cardiovascular disease risk is highest among South Asian and Filipino adults but lowest among Chinese, Japanese, and Korean adults. This scientific statement discusses the biological pathway of type 2 diabetes and the possible role of genetics in type 2 diabetes and atherosclerotic cardiovascular disease among Asian American adults. Challenges to provide evidence-based recommendations included the limited data on Asian American adults in risk prediction models, national surveillance surveys, and clinical trials, leading to significant research disparities in this population. The large disparity within this population is a call for action to the public health and clinical health care community, for whom opportunities for the inclusion of the Asian American subgroups should be a priority. Future studies of atherosclerotic cardiovascular disease risk in Asian American adults need to be adequately powered, to incorporate multiple Asian ancestries, and to include multigenerational cohorts. With advances in epidemiology and data analysis and the availability of larger, representative cohorts, furthering refining the Pooled Cohort Equations, in addition to enhancers, would allow better risk estimation in segments of the population. Last, this scientific statement provides individual- and community-level intervention suggestions for health care professionals who interact with the Asian American population.

Omega-3 fatty acids and cognitive function.

PURPOSE OF REVIEW: The aim is to provide an update on omega-3 polyunsaturated fatty acids (n-3 PUFA) in preventing cognitive decline and dementia. RECENT FINDINGS: Prospective studies and three new meta-analyses suggest that fish or n-3 PUFA intake are associated with a reduction in development of mild cognitive decline and Alzheimer's disease. Supplementation with docosahexaenoic acid (DHA) in randomized controlled trials (RCTs) in those with mild cognitive impairment showed benefit on cognitive decline, whereas there was no benefit in Alzheimer's disease. In cognitively healthy individuals with clinical coronary artery disease (CAD), 3.36 g EPA and DHA daily slowed cognitive ageing by 2.5 years. Of 15 RCTs in cognitively healthy individuals age more than 55 years, seven reported benefit, whereas eight did not. Potential mechanisms for differences in outcomes include dose, trial duration, apolipoproteinE genotype, sex, stage and rate of cognitive decline, cognitive testing employed and individual characteristics. The downstream product of DHA, neuroprotectin D1, may be involved in beneficial effects. SUMMARY: Patients with early memory complaints or a family history of dementia and those with CAD should be counselled on the potential benefits of fish intake and supplementation with n-3 PUFA. ApolipoproteinE4 carriers may especially benefit from DHA supplementation prior to development of cognitive decline.

Omega-3 fatty acids, subclinical atherosclerosis, and cardiovascular events: Implications for primary prevention.

BACKGROUND AND AIMS: High-dose eicosapentaenoic acid (EPA) therapy was beneficial in high-risk patients without clinical cardiovascular disease (CVD). Whether higher plasma levels of EPA and docosahexaenoic acid (DHA) have similar benefits in those without subclinical CVD is unclear. We aim to evaluate the interplay between plasma omega-3 fatty acids and coronary artery calcium (CAC) in relation to CVD events. METHODS: We examined 6568 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with plasma EPA and DHA levels and CAC measured at baseline. The primary outcome was incident CVD events (myocardial infarction, angina, cardiac arrest, stroke, CVD death). Hazard ratios for the primary outcome were adjusted for potential confounder using Cox regression. RESULTS: Mean ± SD age was 62.1 ± 10.2 years and 52.9% were females. The median follow-up time was 15.6 years. Higher loge(EPA) (adjusted hazard ratio, aHR = 0.83; 95% CI, 0.74-0.94) and loge(DHA) (aHR = 0.79; 95% CI, 0.66-0.96) were independently associated with fewer CVD events. The difference in absolute CVD event rates between lowest vs. highest EPA tertile increased at higher CAC levels. The adjusted HR for highest vs. lowest EPA tertile within CAC = 0 was 1.02 (95% CI, 0.72-1.46), CAC = 1-99 was 0.71 (95% CI, 0.51-0.99), and CAC≥100 was 0.67 (95% CI, 0.52-0.84). A similar association was seen in tertiles of DHA by CAC category. CONCLUSIONS: In an ethnically diverse population free of clinical CVD, higher plasma omega-3 fatty acid levels were associated with fewer long-term CVD events. The absolute decrease in CVD events with higher omega-3 fatty acid levels was more apparent at higher CAC scores.

Diverging levels of COVID-19 governmental response satisfaction across middle eastern Arab countries: a multinational study.

BACKGROUND: Public acceptance of governmental measures are key to controlling the spread of infectious diseases. The COVID-19 pandemic has placed a significant burden on healthcare systems for high-income countries as well as low- and middle-income countries (LMICs). The ability of LMICs to respond to the challenge of the COVID-19 pandemic has been limited and may have affected the impact of governmental strategies to control the spread of COVID-19. This study aimed to evaluate and compare public opinion on the governmental COVID-19 response of high and LMICs in the Middle East and benchmark it to international countries. METHODS: An online, self-administered questionnaire was distributed among different Middle Eastern Arab countries. Participants' demographics and level of satisfaction with governmental responses to COVID-19 were analyzed and reported. Scores were benchmarked against 19 international values. RESULTS: A total of 7395 responses were included. Bahrain scored highest for satisfaction with the governmental response with 38.29 ± 2.93 on a scale of 40, followed by the Kingdom of Saudi Arabia (37.13 ± 3.27), United Arab Emirates (36.56 ± 3.44), Kuwait (35.74 ± 4.85), Jordan (23.08 ± 6.41), and Lebanon (15.39 ± 5.28). Participants' country of residence was a significant predictor of the satisfaction score (P < 0.001), and participants who suffered income reduction due to the pandemic, had a history of SARS-CoV-2 infection, and held higher educational degrees had significantly lower satisfaction scores (P < 0.001). When benchmarked with other international publics, countries from the Gulf Cooperation Council had the highest satisfaction level, Jordan had an average score, and Lebanon had one of the lowest satisfaction scores. CONCLUSION: The political crisis in Lebanon merged with the existing corruption were associated with the lowest public satisfaction score whereas the economical instability of Jordan placed the country just before the lowest position. On the other hand, the solid economy plus good planning and public trust in the government placed the other countries of the Gulf Cooperation Council on top of the scale. Further investigation is necessary to find out how the governments of other low-income countries may have handled the situation wisely and gained the trust of their publics. This may help convey a clearer picture to Arab governments that have suffered during the pandemic.

Comprehensive Review of Cardiovascular Complications of Coronavirus Disease 2019 and Beneficial Treatments.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 and was first reported in December 2019 in Wuhan, China. Since then, it caused a global pandemic with 212,324,054 confirmed cases and 4,440,840 deaths worldwide as of August 22, 2021. The disease spectrum of COVID-19 ranges from asymptomatic subclinical infection to clinical manifestations predominantly affecting the respiratory system. However, it is now evident that COVID-19 is a multiorgan disease with a broad spectrum of manifestations leading to multiple organ injuries including the cardiovascular system. We review studies that have shown that the relationship between cardiovascular diseases and COVID-19 is indeed bidirectional, implicating that preexisting cardiovascular comorbidities increase the morbidity and mortality of COVID-19, and newly emerging cardiac injuries occur in the settings of acute COVID-19 in patients with no preexisting cardiovascular disease. We present the most up-to-date literature summary to explore the incidence of new-onset cardiac complications of coronavirus and their role in predicting the severity of COVID-19. We review the association of elevated troponin with the severity of COVID-19 disease, which includes mild compared to severe disease, in nonintensive care unit compared to intensive care unit patients and in those discharged from the hospital compared to those who die. The role of serum troponin levels in predicting prognosis are compared in survivors and non-survivors. The association between COVID-19 disease and myocarditis, heart failure and coagulopathy are reviewed. Finally, an update on beneficial treatments is discussed.

Nonalcoholic Fatty Liver Disease and Cardiovascular Risk: A Scientific Statement From the American Heart Association.

Nonalcoholic fatty liver disease (NAFLD) is an increasingly common condition that is believed to affect >25% of adults worldwide. Unless specific testing is done to identify NAFLD, the condition is typically silent until advanced and potentially irreversible liver impairment occurs. For this reason, the majority of patients with NAFLD are unaware of having this serious condition. Hepatic complications from NAFLD include nonalcoholic steatohepatitis, hepatic cirrhosis, and hepatocellular carcinoma. In addition to these serious complications, NAFLD is a risk factor for atherosclerotic cardiovascular disease, which is the principal cause of death in patients with NAFLD. Accordingly, the purpose of this scientific statement is to review the underlying risk factors and pathophysiology of NAFLD, the associations with atherosclerotic cardiovascular disease, diagnostic and screening strategies, and potential interventions.

The role of HDL- and non-HDL-related parameters in cell-cholesterol efflux capacity.

BACKGROUND AND AIMS: The regulation of cell-cholesterol efflux is not completely understood. Our aim was to assess the role of HDL- and non-HDL-related parameters in ATP-binding cassette transporter-A1 (ABCA1) and scavenger receptor class B-type-I (SRBI) cell-cholesterol efflux capacity (CEC) in coronary heart disease (CHD) cases and controls. METHODS: Lipids and apoA-I-containing HDL particles (by 2D gel-electrophoresis and immunodetection) were measured in 534 statin-treated CHD patients and in 1076 age-, gender-, and BMI-matched controls. ABCA1-CEC and SRBI-CEC were measured in apoB-depleted serum of 100 cases and 100 controls. RESULTS: Cases had significantly higher concentrations of preß-1 particles (88%) and ABCA1-CEC (34%) compared to controls. ABCA1-CEC was positively correlated with the concentrations of preß-1 particles, triglycerides, small-dense (sd) LDL-C, and LDL-C in both cases and controls. Moreover, both the concentration and the functionality of preß-1 particles (ABCA1-CEC/mg preß-1) were positively associated with the concentrations of sdLDL-C and triglycerides. Cases had 27% lower levels of large HDL particles but similar SRBI-CEC compared to controls. SRBI-CEC was correlated positively with HDL-C, apoA-I, and large-HDL particle levels. However, the functionality of large-HDL particles (SRBI-CEC/mg large particles) was significantly and positively correlated with the preß-1/α-1 ratio, sdLDL-C, and triglycerides. CONCLUSIONS: CHD patients have significantly higher concentration, but less functional preß-1 particles in term of cholesterol efflux capacity compared to controls. Triglyceride-rich lipoproteins have significant influence on either the concentration or the functionality or both of HDL particles and consequently HDL-CEC.

Clinical characteristics and cardiovascular outcomes among young patients with acute myocardial infarction in Kerala, India: A secondary analysis of ACS QUIK trial.

Background: Limited data exist on the risk profile and outcomes among young patients with acute myocardial infarction(AMI) in low-and middle-income countries(LMICs). This study explored differences in the clinical characteristics, medical care, and outcomes of AMI in young adults in India with a subanalysis focusing on sex disparities amongst the young. Methods: Using the Acute Coronary Syndrome Quality Improvement in Kerala trial database, we compared baseline characteristics, management, and outcomes amongst the young patients(≤50 years) and their older counterparts. The primary outcomes were the rates of in-hospital and 30-day composite of in-hospital major adverse cardiovascular events(MACE). Results: Of the 21,374 adults enrolled, 4762(22%) were young, of which 614 (12.9%) were females. Young patients with AMI were more likely to be smokers(41.9% vs. 27.8%;P < 0.001) and undergo coronary angiography (66.3%vs.57.3%;P < 0.001) and percutaneous coronary intervention (PCI)(57.5% vs. 47.0%;P < 0.001), compared to older patients. After adjustment for potential confounders, younger patients had a lower likelihood of in-hospital (RR = 0.49; 95%CI 0.40-0.61;P < 0.001) and 30-day MACE (RR = 0.54; 95%CI 0.46-0.64;P < 0.001). Subgroup analysis comparing young males and females revealed worse cardiovascular risk profile among young women except for smoking. In-hospital MACE(RR = 1.60; 95%CI, 1.0-2.45;P = 0.048) were higher for young women compared to men. Conclusion: Young AMI patients had higher prevalence of modifiable risk factors, were more likely to receive reperfusion therapy, and had better short and intermediate outcomes, compared to older patients. Compared to young men with AMI, young women had worse cardiovascular risk profile, were less likely to be treated with diagnostic angiography or PCI and experienced higher in-hospital death and MACE.

Association Between Omega-3 Fatty Acid Levels and Risk for Incident Major Bleeding Events and Atrial Fibrillation: MESA.

Background Randomized trials of pharmacologic strength omega-3 fatty acid (n3-FA)-based therapies suggest a dose-dependent cardiovascular benefit. Whether blood n3-FA levels also mediate safety signals observed in these trials, such as increased bleeding and atrial fibrillation (AF), remains uncertain. We hypothesized that higher baseline n3-FA levels would be associated with incident bleeding and AF events in MESA (Multi-Ethnic Study of Atherosclerosis), which included a population free of clinical cardiovascular disease at baseline. Methods and Results We examined the association between baseline plasma n3-FA levels (expressed as percent mass of total fatty acid) with incident bleeding and AF in MESA, an ongoing prospective cohort study. Bleeding events were identified from review of hospitalization International Classification of Diseases, Ninth Revision (ICD-9), and International Classification of Diseases, Tenth Revision (ICD-10), codes, and AF from participant report, discharge diagnoses, Medicare claims data, and study ECGs performed at MESA visit 5. Separate multivariable Cox proportional hazard modeling was used to estimate hazard ratios of the association of continuous n3-FA (log eicosapentaenoic acid [EPA], log docosahexaenoic acid [DHA], log [EPA+DHA]) and incident hospitalized bleeding events and AF. Among 6546 participants, the mean age was 62.1 years and 53% were women. For incident bleeding, consistent statistically significant associations with lower rates were seen with increasing levels of EPA and EPA+DHA in unadjusted and adjusted models including medications that modulate bleeding risk (aspirin, NSAIDS, corticosteroids, and proton pump inhibitors). For incident AF, a significant association with lower rates was seen with increasing levels of DHA, but not for EPA or EPA+DHA. Conclusions In MESA, higher plasma levels of n3-FA (EPA and EPA+DHA, but not DHA) were associated with significantly fewer hospitalized bleeding events, and higher DHA levels (but not EPA or EPA+DHA) with fewer incident AF events.

ω-3 Ethyl ester results in better cognitive function at 12 and 30 months than control in cognitively healthy subjects with coronary artery disease: a secondary analysis of a randomized clinical trial.

BACKGROUND: Omega-3 (n-3) fatty acids have shown benefit in cognitively impaired subjects, but the effect on cognitively healthy older subjects is unclear. OBJECTIVES: Our aim was to determine if long-term, high-dose ω-3 ethyl esters, EPA (20:5n-3) and DHA (22:6n-3), prevent deterioration of cognitive function in cognitively healthy older adults. METHODS: A total of 285 subjects with stable coronary artery disease (CAD) on statin treatment were randomly assigned to 3.36 g EPA and DHA or none (control) for 30 mo. Cognitive function was assessed in all 285 subjects at baseline and in 268 and 250 subjects who returned at 12- and 30-mo follow-up, respectively, with neuropsychological testing as a prespecified secondary outcome. A completer's analysis, along with a sensitivity analysis carrying forward the last observation, was performed. RESULTS: Over the 30-mo period, subjects randomly assigned to EPA and DHA had significantly better scores than control for verbal fluency, language, and memory (mean: 1.08; 95% CI: 0.25, 1.91; P = 0.011) and 2 tests of visual-motor coordination (mean: -2.95; 95% CI: -5.33, -0.57; P = 0.015 and mean: -9.44; 95% CI: -18.60, -0.30; P = 0.043, respectively). The better scores for EPA and DHA were due to an improvement at 12 mo compared with baseline in verbal fluency, language, and memory (P = 0.047) and 2 tests of visual-motor coordination (P = 0.033 and P < 0.001, respectively), whereas control had no change. Post hoc analyses indicated no difference by age, sex, or diabetes status. CONCLUSIONS: Cognitively healthy older adults with stable CAD randomly assigned to high-dose EPA and DHA had improved cognitive function over a 30-mo period compared with control. These findings may be especially important for CAD patients because CAD is a risk factor for cognitive decline.This trial was registered at clinicaltrials.gov as NCT01624727.